PROJECT SUMMARY/ABSTRACT The scientific theme of the proposed Center for Musculoskeletal Disease Research (CMDR) at the University of Arkansas for Medical Sciences (UAMS) is that molecular and genetic analysis of diseases that involve the skeleton will lead to a better understanding of their causes and will support development of novel therapies. Four research projects, each led by a junior investigator, will investigate different conditions that lead to damage of the musculoskeletal system. Each of these projects will employ high-throughput technologies to generate large datasets for genome-wide characterization of experimental samples. These datasets will contribute to deep molecular characterization and enable comprehensive monitoring of cellular processes and advance understanding of biological systems. However, the amount of data generated is vast, its dimensionality is high, and it is typically difficult to handle. Therefore, effective extraction of meaningful information from these datasets will require personnel with the appropriate expertise and access to the necessary computational facilities. To address these needs, we will establish a new Bioinformatics Core at UAMS for computational analyses of large data sets that assembles the personnel, equipment, and computational algorithms required to meet the needs of the Project Leaders and CMDR members (Aim 1). We will provide bioinformatics services to these investigators and develop customized new services to meet their evolving needs via custom bioinformatics analysis pipelines derived from up-to-date computational algorithms and biological knowledge databases that fit the needs of the specific research project (Aim 2). We will also provide training and education related to the use of bioinformatics so that Project Leaders and other users will be better able to understand and use the principles and concepts of bioinformatics methods related to their research subjects (Aim 3). The Bioinformatics Core will consist of personnel who have strong bioinformatics skills, appropriate biological knowledge, and experience working with biologists. The team will provide advanced bioinformatics/systems biology guidance and analyses at all stages of genome-wide experiments. Project Leaders and other CMDR members will acquire bioinformatic skills and expertise that will have long-term benefits for them individually and the Center as a whole. In the short- term, the Bioinformatics Core will enable Project Leaders to rapidly and efficiently integrate the results obtained from the other CMDR cores: the Genetic Models Core (Core B) and the Bone Histology and Imaging Core (Core C). In turn, bioinformatic analyses will prompt the creation of new genetic models and guide interpretation of imaging and histologic analyses. This iterative process will result in synergy that would be difficult to achieve without the coordinated leadership and access provided by the CMDR. Overall, access to the Bioinformatics Core's cutting-edge resources, and the critical mass of investigators that it supports, will greatly strengthen the research communities at UAMS and in Arkansas.